The overall objective of this proposal is to cooperate with the Central Nervous System Cancer Consortium (CNSCC) to perform phase l and Il clinical evaluations of promising new chemotherapeutic agents for the treatment of primary central nervous system (CNS) malignancies and to perform ancillary laboratory studies of aspects of CNS tumor biology with potential clinical implications. In 1993 in North America it is estimated that over 17,500 new cases of primary CNS tumor will be diagnosed and over 12,100 will die of this disease. The majority of these will have a primary malignant glioma. Current available treatment for the vast majority of these patients are inadequate. It is the goal of this proposal to conduct therapeutic studies of new treatments of primary CNS malignancies in adults to evaluate and develop more effective treatments. The specific aims of this proposal are: to accrue patients to the CNS Cancer Consortium protocol in accordance with the goals of this RFA; to collect, store and distribute tissue as related to the laboratory needs of the CNS Cancer Consortium in accordance with the goals of the protocols for this RFA; to augment brain tumor tissue banking activity at this center to support the CNSCC laboratory needs and support ongoing research at this center including studies of the molecular genetic basis of glioma predisposition, induction and progression, and the responses of malignant gliomas to chemotherapy in relation to their cell of origin (ie. lineage of origin). Initially we will activate and participate in three clinical trials with the CNS Cancer Consortium: a phase I study of estramustine for recurrent glioblastoma and anaplastic astrocytoma; a phase II study of topotecan with external beam radiotherapy for biopsy only glioblastoma; and a phase II study of pre-irradiation BCNU with measurement of brain tumor alkyltransferase (AT) levels for newly diagnosed glioblastoma and anaplastic astrocytoma. Future studies will include phase I studies of penicillamine, 0(6)-benzylguanine with BCNU, and phase II studies of temozolomide. The London Regional Cancer Center (LRCC) is a regional cancer treatment facility and the sole radiotherapy unit in Central Southwestern Ontario (estimated population, 1.4 million). It is a modern fully accredited 125,000 sq ft ambulatory care facility, seeing 3800 new cancer patients and 40,000 followups yearly. The center has complete radiotherapy, chemotherapy, and pharmacy facilities. The LRCC is a Division of the Ontario Treatment and Research Foundation and is affiliated with the University of Western Ontario and its three teaching hospitals in London. The LRCC is the region's principal oncology center and the University's Department of Clinical Neurological Sciences, is the region's principal neuro-diagnostic and neurosurgical center. Three MRI units and 5 CT scanners are available in the city. The centralized nature of tertiary health care in Ontario means that Drs. David R.Macdonald and J.Gregory Cairncross(based at the LRCC) see all patients in the region with anaplastic glioma. Over 100 new primary brain tumor patients are seen each year, 50-60 of which are malignant gliomas in adults. Over 30 brain tumor patients yearly are entered onto cooperative clinical trials, including CNSCC studies. A brain tumor tissue bank has been established at Victoria Hospital. Thus the LRCC has the experience and resources to achieve the objectives of this proposal.